Methods, devices and systems for transcatheter mitral valve replacement in a double-orifice mitral valve

ABSTRACT

In various embodiments, provided herein are methods, devices and systems for transcatheter mitral valve replacement in a double-orifice mitral valve. These methods, devices and systems are used to treat patients with mitral valve disease, particularly those who have had failed edge-to-edge leaflet repair, or patients presently considered anatomically unsuitable for edge-to-edge leaflet repair alone.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a National Phase of International Application No.PCT/US2014/069849 filed Dec. 11, 2014, currently pending, whichdesignated the U.S. and that International Application was publishedunder PCT Article 21(2) in English, which also includes a claim ofpriority under 35 U.S.C. § 119(e) to U.S. provisional patent applicationNo. 61/914,591 filed Dec. 11, 2013, the entirety of which is herebyincorporated by reference.

FIELD OF INVENTION

This invention relates to methods, devices and systems for transcathetermitral valve replacement in a double-orifice mitral valve, which may beused to treat mitral valve diseases.

BACKGROUND OF THE INVENTION

All publications cited herein are incorporated by reference in theirentirety to the same extent as if each individual publication or patentapplication was specifically and individually indicated to beincorporated by reference. The following description includesinformation that may be useful in understanding the present invention.It is not an admission that any of the information provided herein isprior art or relevant to the presently claimed invention, or that anypublication specifically or implicitly referenced is prior art.

Valvular heart disease is characterized by damage to or a defect in oneof the four heart valves: the mitral, aortic, tricuspid or pulmonary.The mitral and tricuspid valves control the flow of blood between theatria and the ventricles (the upper and lower chambers of the heart).The pulmonary valve controls the blood flow from the heart to the lungs,and the aortic valve governs blood flow between the heart and the aorta,and thereby to the blood vessels in the rest of the body. The mitral andaortic valves are most frequently affected by valvular heart disease.

Transcatheter valve therapies are one treatment option for patients. Forexample, transcatheter aortic valve replacement (TAVR—also known as TAVIor transcatheter aortic valve implantation) is a procedure for patientswith severe symptomatic aortic stenosis (narrowing of the aortic valveopening) who are not candidates for traditional open chest surgery orare high-risk operable candidates. In these procedures, a replacementvalve is inserted percutaneously using a catheter and implanted in theorifice of the native aortic valve. Replacement valves may be artificial(prosthetic valves) or made from animal tissue (bioprosthetic valves).The type of replacement valve selected depends on the patient's age,condition, and the specific valve affected.

The most common form of valvular heart disease is mitral regurgitation(MR), in which the two leaflets (anterior and posterior) of the mitralvalve do not close properly when the heart pumps out blood. Oneprocedure for MR is edge-to-edge leaflet repair. This procedure uses asuture, a percutaneous suture (e.g. Edwards' Mobius) or a clip (e.g.Abbott's Mitraclip) to bring the anterior and posterior leafletstogether at their middle points, creating a “double-orifice” mitralvalve. As a result, leaflet coaptation is re-established to reduce MR.Although often effective, this surgery still has a relatively highfailure rate, due to either residual MR or, less commonly, increasedtransmitral flow gradients. Moreover, many patients are consideredunsuitable for double orifice repair as there may be anatomical featuresthat predict failure.

SUMMARY OF THE INVENTION

To treat subjects with mitral valve diseases (for example, MR patientswho have had failed edge-to-edge leaflet repair), described herein is adouble-orifice transcatheter mitral valve replacement (DO-TMVR) device.In some embodiments, this DO-TMVR device has a double-orifice structurethat anchors to a patient's double-orifice mitral valve. A Y-shapeddelivery system can be used to deliver the DO-TMVR device into thedouble-orifice mitral valve from the atrium or ventricle.

The following embodiments and aspects thereof are described andillustrated in conjunction with systems, compositions and methods whichare meant to be exemplary and illustrative, not limiting in scope.

In various embodiments, provided herein is a device for transcathetermitral valve replacement. The device comprises: a first replacementheart valve having a first atrial side and a first ventricular side; anda second replacement heart valve having a second atrial side and asecond ventricular side.

In various embodiments, provided herein is a device for transcathetermitral valve replacement. The device comprises: a first replacementheart valve having a first atrial side and a first ventricular side; asecond replacement heart valve having a second atrial side and a secondventricular side; and a delivery catheter. In some embodiments, thedelivery catheter has an inverted Y-shaped inflatable balloon at itsdistal end. In other embodiments, the delivery catheter has an invertedY-shaped enclosing sheath at its distal end.

In various embodiments, provided herein is a device for transcathetermitral valve replacement. The device comprises: a first replacementheart valve having a first atrial side and a first ventricular side; asecond replacement heart valve having a second atrial side and a secondventricular side; and two guide wires, wherein a delivery catheter canbe inserted over the two guide wires.

In various embodiments, provided herein is a device for transcathetermitral valve replacement. The device comprises: a first replacementheart valve having a first atrial side and a first ventricular side; asecond replacement heart valve having a second atrial side and a secondventricular side; and a sheath, wherein a delivery catheter can beinserted into the sheath.

In various embodiments, provided herein is a device for transcathetermitral valve replacement. The device comprises: a first replacementheart valve having a first atrial side and a first ventricular side; asecond replacement heart valve having a second atrial side and a secondventricular side; and a connector for connecting the two replacementvalves, wherein the two replacement valves can be indirectly connectedvia the connector.

In an embodiment, the two replacement heart valves can be unconnectedand anchored separately to the tissue formed by each of the two orificesof the double orifice. In some embodiments, if the residualregurgitation or stenosis is localized to one of the two orifices, asingle prosthetic or bioprosthetic valve may be anchored to the tissueformed by that orifice, with the second orifice left without aprosthetic or bioprosthetic valve. In some embodiments, the tworeplacement heart valves can be connected on their atrial and/orventricular sides. In accordance with the present invention, the tworeplacement heart valves can be connected prior to or after deploymentof the device. As non-limiting examples, the two replacement heartvalves may be indirectly connected via a hinge, click-and-lock system,tongue-and-groove system, interlocking structure, clasp, hook, ring,bolts, nut, screw, nail, fastener, magnet, mortise and/or tenon. In anembodiment, the two replacement heart valves may not be directlyconnected to each other; the two replacement heart valves may not extendfrom each other; the two replacement heart valves may not be heldtogether by a frame or gasket; and/or no frame or gasket may surroundboth replacement heart valves.

In some embodiments, the two replacement valves can be prostheticvalves, bio-prosthetic valves, or a combination. In accordance with thepresent invention, the two replacement valves can be self-expandablevalves, balloon expandable valves, a combination, or other suitablereplacement valves. In some embodiments, the cross sections of the tworeplacement valves can be circles, ellipses, a combination, or othersuitable shapes. In some embodiments, the cross sections of the tworeplacement valves can be two D shapes with their straight sidesopposing each other.

In some embodiments, both or one of the two replacement valves cancomprise stent frames made of iron, platinum, titanium, nickel,chromium, cobalt, magnesium, stainless steel, nitinol (nickel-titanium),nickel-chromium, cobalt-chromium, or platinum-iridium, or a combinationthereof. In some embodiments, both or one of the two replacement valvescomprises one, two, three, or more leaflets.

In various embodiments, provided herein is a method for transcathetermitral valve replacement. The method comprises the following steps: (1)identifying a subject having a double-orifice mitral valve; (2)providing a device as described herein; and (3) delivering the device tothe double-orifice mitral valve.

In various embodiments, provided herein is a method for treatingresidual MR after a double orifice repair or, less commonly, mitralstenosis (MS) after a double orifice repair. In various embodiments, thecreation of a double orifice may facilitate the DO-TMVR in a patientthat would normally be considered anatomically unsuitable for a doubleorifice repair due to a high anticipated risk of failure. The methodcomprises the following steps: (1) performing an edge-to-edge repair ofa mitral valve in a subject, thereby creating a double-orifice mitralvalve; (2) establishing that there is significant residual mitral valvedisease; (3) providing a device as described herein; and (4) deliveringthe device to the double-orifice mitral valve.

In various embodiments, provided herein is a method for treatingsubjects with mitral valve diseases (for example, MR, residual MR, orMS). The method comprises the following steps: (1) performing anedge-to-edge repair of a mitral valve in a subject, thereby creating adouble-orifice mitral valve; (2) assessing MR in the subject after theedge-to-edge repair; (3) if the edge-to-edge repair does not effectivelytreat MR and/or MS in the subject, providing a device as describedherein; and (4) delivering the device to the double-orifice mitralvalve. In accordance with the present invention, MR can be assessed witha variety of techniques and procedures known to one of ordinary skill inthe art, including but not limited to, transthoracic and transesophagealechocardiography, angiography, MRI and transcatheter hemodynamicassessment. More details are described in Zoghbi et al. (Recommendationsfor evaluation of the severity of native valvular regurgitation withtwo-dimensional and Doppler echocardiography, American Society ofEchocardiography, J Am Soc Echocardiogr., 2003 July; 16(7):777-802),which is incorporated by reference herein in its entirety.

In accordance with the present invention, the device can be deliveredtransseptally or transapically. Still in accordance with the presentinvention, the subject can be a human or a mammal.

BRIEF DESCRIPTION OF FIGURES

Exemplary embodiments are illustrated in the referenced figures. It isintended that the embodiments and figures disclosed herein are to beconsidered illustrative rather than restrictive.

FIGS. 1A1, depicts a cross section of the heart including the leftatrium and left ventricle. FIG. 1A2 depicts a cross section of themitral valve with the anterior mitral leaflet and posterior mitralleaflet properly closed and sealed to prevent backflow. FIG. 1B1 depictsa cross section of the heart with mitral regurgitation. The arrowsillustrate an example of back flow from the left ventricle to the leftatrium through a leaky mitral valve. MR is often due to malcoaptation ofthe anterior and posterior leaflets of the mitral valve, or where theanterior and posterior leaflets do not fit together properly to form aseal. In a healthy mitral valve, normal coaptation prevents MR duringsystole (FIGS. 1A1 and 1A2). FIGS. 1B1, depicts a cross section of theheart including the left atrium and left ventricle. FIG. 1B2 depicts across section of the mistral valve. In a diseased mitral valve,malcoaptation results in jets of MR directed into the left atrium duringsystole (FIGS. 1B1 and 1B2). AML refers to anterior mitral leaflet; PMLrefers to posterior mitral leaflet; LA refers to left atrium; and LVrefers to left ventricle.

FIG. 1C1 depicts a cross section of the heart including a leaking mitralvalve. FIG. 1C2 depicts an example of a cross section of a mitral valvethat has undergone an edge-to-edge repair procure. An edge-to-edgerepair (for example, applying an Alfieri surgical stitch, (e.g., EDWARDSLIFESCIENCES' MOBIUS percutaneous stitch, or ABBOTT's MITRACLIP)involves the attachment of the center of the leaflets to each other asillustrated in the cross section of the valve shown in FIG. 1C2. Thisprocedure brings the leaflets closer together and thereby reduces MR.However, this procedure may not completely address the MR, or patientmay be excluded from having this procedure because of a high chance offailure. The present disclosed devices and methods capitalize on thepartial apposition of the anterior and posterior mitral leaflets and usethe connected tissue at their middle points as an anchor for atranscatheter mitral valve repair (TMVR) device, that is, adouble-orifice TMVR device (DO-TMVR).

FIG. 1D depicts, in accordance with various embodiments, a perspectiveview of a deployed DO-TMVR comprising two replacement valves (101 and102). In this non-limiting example, the two replacement valves (101 and102) are both cylindrical.

FIG. 1E depicts, in accordance with various embodiments, a perspectiveview of a DO-TMVR device comprising two replacement valves (101 and102). In this non-limiting example, the two replacement valves (101 and102) are shaped as two opposing D shapes.

FIGS. 2A-E depict cross sections of the heart, in accordance withvarious embodiments, a DO-TMVR device comprising two balloon-expandablereplacement valves and a transseptal procedure of deploying the DO-TMVRdevice and a method of surgically implanting the DO-TMVR device. FIG. 2Adepicts a cross section of a heart with a transseptal catheter 208 fordelivery of a DO-TMVR device being advanced by entering through thefemoral leg vein through to the right atrium. FIG. 2B depicts a firstguide wire 201, a second guide wire 202, a sheath 203. FIG. 2C depicts adelivery catheter 204, and an inverted Y-shaped inflatable balloon atthe delivery catheter's distal end. FIG. 2D also depicts a transseptalcatheter 208, and two replacement valves 101 and 102 in a DO-TMVRdevice. Also illustrated is a connector 103 connecting replacement valve101 to replacement valve 102. FIG. 2E also depicts a cross section of aheart with a transseptal catheter 208, and two replacement valves 101and 102 in a DO-TMVR device.

FIGS. 3A-E depict, in accordance with various embodiments, a crosssection of a heart, a DO-TMVR device comprising two balloon-expandablereplacement valves, and a transapical procedure of deploying the DO-TMVRdevice. FIG. 3A illustrates a cross section of the heart and the entrypath for delivery of the DO-TMVR device. FIG. 3B illustrates thedelivery catheter transapically inserted into the left ventricle and afirst guide wire 201 a second guidewire 202, and a sheath 203. FIG. 3Cillustrates the DO-TMVR device deployed from the catheter across themitral valve. FIG. 3D illustrates the DO-TMVR device being furtherdeployed in a cross section of the heart. FIG. 3E illustrates theDO-TMVR device being further deployed in a cross section of the heart.

FIGS. 4A-E depict, a cross section of a heart in accordance with variousembodiments, a DO-TMVR device comprising two self-expandable replacementvalves, and a transseptal procedure of deploying the DO-TMVR device.FIG. 4A depicts the delivery of the catheter from the femoral veinthrough the right atrium and the delivery path through the septum. FIG.4B illustrates the sheath 203 advanced through the septum of the heartinto the left atrium. FIG. 4C depicts the DO-TMVR device being deployedin the mitral valve space. FIG. 4D is a cut-away view of a replacementvalve 102 enclosed in a branch of the inverted Y-shaped enclosing sheath207 (i.e., in the enclosing cap 212 placed at the distal end of thecatheter 210). In the delivery catheter, two catheters 210 and 211 areinserted into a cover 209. The two replacement valves 101 and 102 aremounted near the distal ends of the two catheters 210 and 211. Furtherdistal to the two replacement valves 101 and 102, two enclosing caps 212and 213 are placed at the distal ends of the two catheters 210 and 211.The two enclosing caps 212 and 213 enclose the two replacement valves101 and 102 to keep them compressed. FIG. 4E depicts the DO-TMVR devicebeing deployed in the mitral valve space.

FIGS. 5A-5E depict cross sectional views of the heart, in accordancewith various embodiments, DO-TMVR devices comprising two self-expandablereplacement valves, and a transapical procedure of deploying the DO-TMVRdevice. FIG. 5A depicts a cross sectional view of the heart. FIG. 5Bdepicts a sheath 203 transapically advanced into the left atrium. FIG.5C illustrates the DO-TMVR device being deployed in the mitral valve.FIG. 5D is a cut-away view of a replacement valve 102 enclosed in abranch of the inverted Y-shaped enclosing sheath 207 (i.e., in theenclosing cap 212 placed at the distal end of the catheter 210). FIG. 5Eillustrates the DO-TMVR device being deployed in the mitral valve

FIGS. 6A-D depict various perspective and cross sectional views of anembodiment of a DO-TMVR device comprising two balloon-expandablereplacement valves. FIG. 6A illustrates a perspective view of anembodiment of a DO-TMVR device for deployment transapically, including aconnector 103 between the left valve 103 and right valve 104. Asillustrated in FIG. 6A, for a DO-TMVR device to be deployedtransapically, there may be a connector on the left ventricular sideconnecting the two replacement valves. FIG. 6B illustrates a perspectiveview of an embodiment of a DO-TMVR device for transseptical deployment,including a connector 103 between the left valve 103 and right valve104. As illustrated in FIG. 6B, for a DO-TMVR device to be deployedtransseptally, there may be a connecting means on the left atrial sideconnecting the two replacement valves. FIG. 6C illustrates a crosssectional view of an embodiment of a DO-TMVR device, including openleaflets 106. FIG. 6D illustrates a cross sectional view of anembodiment of a DO-TMVR device, including closed leaflets 106).

FIGS. 7A-D depict various perspective and cross sectional views of anembodiment of a DO-TMVR device comprising two self-expandablereplacement valves. FIG. 7A illustrates a perspective view of anembodiment of a DO-TMVR device for deployment transapically, including aconnector 103 between the left valve 103 and right valve 104. Asillustrated in FIG. 7A, for a DO-TMVR device to be deployedtransapically, there may be a connector 103 on the left ventricular sideconnecting the two replacement valves. FIG. 7B illustrates a perspectiveview of an embodiment of a DO-TMVR device for deploymenttransseptically, including a connector 103 between the left valve 103and right valve 104. As illustrated in FIG. 7B, for a DO-TMVR device tobe deployed transseptally, there may be a connector on the left atrialside connecting the two replacement valves. FIG. 7C illustrates a crosssectional view of an embodiment of a DO-TMVR device, including openleaflets 106. FIG. 7D illustrates a cross sectional view of anembodiment of a DO-TMVR device, including closed leaflets 106

FIGS. 8A-C depict, in accordance with various embodiments, crosssectional views of three exemplar click-and-lock systems as non-limitingexamples of a connectors for connecting the two replacement valves. FIG.8A illustrates an embodiment of a cross sectional view of aclick-and-lock connection. FIG. 8B illustrates an embodiment of a crosssectional view of a click-and-lock connection. FIG. 8C illustrates afurther embodiment of a cross sectional view of a click-and-lockconnection.

DETAILED DESCRIPTION OF THE INVENTION

All references cited herein are incorporated by reference in theirentirety as though fully set forth. Unless defined otherwise, technicaland scientific terms used herein have the same meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs. Singleton et al., Dictionary of Microbiology and MolecularBiology 3rd ed., J. Wiley & Sons (New York, N.Y. 2001); March, AdvancedOrganic Chemistry Reactions, Mechanisms and Structure 5th ed., J. Wiley& Sons (New York, N.Y. 2001); and Sambrook and Russel, MolecularCloning: A Laboratory Manual 3rd ed., Cold Spring Harbor LaboratoryPress (Cold Spring Harbor, N.Y. 2001), provide one skilled in the artwith a general guide to many of the terms used in the presentapplication.

One skilled in the art will recognize many methods and materials similaror equivalent to those described herein, which could be used in thepractice of the present invention. Indeed, the present invention is inno way limited to the methods and materials described. For purposes ofthe present invention, the following terms are defined below.

Devices and Systems

Various embodiments of a device for a transcatheter mitral valvereplacement. In some embodiments, the device comprises: a firstreplacement heart valve having a first atrial side and a firstventricular side; and a second replacement heart valve having a secondatrial side and a second ventricular side.

In various embodiments, the two replacement heart valves are connectedon their atrial and/or ventricular sides. In various embodiments, thetwo replacement heart valves are connected and various points betweenthe two replacement heart valves including, halfway in between theventricular and atrial sides, ⅓ of the way from the ventricular oratrial side or other suitable positions. In various embodiments, the tworeplacement heart valves are connected prior to or after deployment ofthe device. In various embodiments, the site of connecting the tworeplacement valves and the time of connecting the two replacement valvesmay depend on the access approach employed for device delivery (forinstance, transseptal or transapical delivery).

In various embodiments, the two replacement heart valves are indirectlyconnected via a hinge, click-and-lock system, tongue-and-groove system,interlocking structure, clasp, hook, ring, bolts, nut, screw, nail,fastener, magnet, mortise and/or tenon. In various embodiments, theconnector between the valves may dissolve over time. In someembodiments, the connector may include a tissue anchoring texture. Insome embodiments, the connector may include a U shaped cross sectionother suitable cross section that conforms to the tissue to which itanchors at the center of the mitral valve. In various embodiments, thetwo replacement heart valves are not directly connected to each otherand are individual deployed. In various embodiments, the two replacementheart valves do not extend from each other. In various embodiments, thetwo replacement heart valves are not hold together by a frame or gasket.In various embodiments, no frame or gasket surrounds both replacementheart valves.

In various embodiments, the first replacement heart valve is about 10-55mm in height. In various embodiments, the second replacement heart valveis about 10-55 mm in height.

In various embodiments, the first replacement heart valve is about 10-55mm in diameter. In various embodiments, the second replacement heartvalve is about 10-55 mm in diameter. In some embodiments, either or bothof the two replacement valves can have varying diameters along theirlongitudinal axes.

In various embodiments, the first replacement heart valve is aprosthetic valve or a bio-prosthetic valve. In various embodiments, thesecond replacement heart valve is a prosthetic valve or a bio-prostheticvalve. In various embodiments, the two replacement heart valves areprosthetic valves, bio-prosthetic valves, or combinations thereof. Inaccordance with the present invention, a prosthetic valve is made ofpurely artificial or non-biological materials, and a bioprosthetic valveis made of animal tissues alone or in combination with artificial ornon-biological materials.

In various embodiments, the first replacement heart valve isself-expandable or balloon expandable. In various embodiments the secondreplacement heart valve is self-expandable or balloon expandable. Anexample of a self-expandable is the MEDTRONIC COREVALVE, which isconstructed with a nitinol self-expanding valve stent frame and porcinepericardial leaflets. An example of a balloon-expandable valve includes,but is not limited to, the EDWARDS SAPIEN XT VALVE, which is constructedwith a cobalt-chromium balloon-expandable valve stent frame and bovinepericardial leaflets.

In various embodiments, the cross section of the first and/or secondreplacement valve is a circle or ellipse, oval, or other suitable shapesthat accommodate the mitral valve space. In various embodiments, thecross section of the two replacement valves are both D shapes with theirstraight sides opposing each other.

In various embodiments, the first replacement valves comprises stentframes made of iron, platinum, titanium, nickel, chromium, cobalt,magnesium, stainless steel, nitinol (nickel-titanium), nickel-chromium,cobalt-chromium, or platinum-iridium, or a combination thereof. Invarious embodiments, the second replacement valves comprises stentframes made of iron, platinum, titanium, nickel, chromium, cobalt,magnesium, stainless steel, nitinol (nickel-titanium), nickel-chromium,cobalt-chromium, or platinum-iridium, or a combination thereof.

In various embodiments, the first replacement valve comprises one, two,three, or more leaflets. In various embodiments, the second replacementvalve comprises one, two, three, or more leaflets.

Various embodiments provide for a device for transcatheter mitral valvereplacement. The device comprises: a first replacement heart valvehaving a first atrial side and a first ventricular side; a secondreplacement heart valve having a second atrial side and a secondventricular side; and a delivery catheter. In some embodiments, thedelivery catheter has an inverted Y-shaped inflatable balloon at itsdistal end. In other embodiments, the delivery catheter has an invertedY-shaped enclosing sheath at its distal end.

In accordance with the present invention, the delivery catheter can becomprised of one or more components. As one non-limiting example, thedelivery catheter can be comprised of one inverted Y-shaped catheterwith two inflatable balloons located on the two distal branches of theinverted Y-shaped catheter, and the first and second replacement valvesof a DO-TMVR device are compressed and mounted over the two inflatableballoons. As another non-limiting example, the delivery catheter may becomprised of two inflatable balloon catheters enclosed in a coversheath, with each catheter having an inflatable balloon located near orat its distal end. In some embodiments, the cover sheath enclosessubstantial portions of the two catheters, from their proximal ends tonear the two inflatable balloons. In some embodiments, the distalportions of the two catheters, where the two inflatable balloons arelocated, are not enclosed by the cover sheath. In some embodiments, thedelivery catheter, as a whole, resembles an inverted Y-shape; and thefirst and second replacement valves of a DO-TMVR device are compressedand mounted over the two inflatable balloons. As still anothernon-limiting example, the delivery catheter can be comprised of twocatheters enclosed in a cover sheath. In some embodiments, the first andsecond replacement valves of a DO-TMVR device are compressed and mountednear the distal ends of the two catheters. In some embodiments, furtherdistal to the two replacement valves, two enclosing caps are placed atthe distal ends of the two catheters. In some embodiments, the twoenclosing caps are distal to the two replacement valve. In someembodiments, the two enclosing caps enclose the two replacement valvesto maintain them in compressed status.

In some embodiments, disclosed is a device for transcatheter mitralvalve replacement. The device comprises: a first replacement heart valvehaving a first atrial side and a first ventricular side; a secondreplacement heart valve having a second atrial side and a secondventricular side; and two guide wires, wherein a delivery catheter canbe inserted over the two guide wires.

In some embodiments, disclosed is a device for transcatheter mitralvalve replacement. The device comprises: a first replacement heart valvehaving a first atrial side and a first ventricular side; a secondreplacement heart valve having a second atrial side and a secondventricular side, and a sheath, wherein a delivery catheter can beinserted into the sheath.

In some embodiments, disclosed is a device for transcatheter mitralvalve replacement. The device comprises: a first replacement heart valvehaving a first atrial side and a first ventricular side; a secondreplacement heart valve having a second atrial side and a secondventricular side; and a connecting means for connecting the tworeplacement valves, wherein the two replacement valves can be indirectlyconnected via the connecting means. In some embodiments, disclosed is adevice with two or more connectors. In some embodiments, the connectorcan be located on the left atrial side, the left ventricular side, or onboth left atrial and left ventricular sides. The connector may beconnected prior to or after deployment of a DO-TMVR device. Variousconnectors can be used to connect the two replacement valves. Examplesof the connectors include but are not limited to a hinge, click-and-locksystem, tongue-and-groove system, interlocking structure, clasp, hook,ring, bolts, nut, screw, nail, fastener, magnet, mortise and/or tenon.Other examples may be found in US 20100185275 A1 and U.S. Pat. No.5,250,071, which are incorporated herein by reference as a whole. Insome embodiments, the connector comprises two or more components, forexample, a click-and-lock system or a tongue-and-groove system. In otherembodiments, the connector comprises only one component, for example, abridge, string, wire, beam or joist.

Suitable examples of guide wires, sheaths, and catheters that may beutilized with the presently disclosed devices, systems and methodsdescribed herein will be apparent to a person of skill in the art.Examples of suitable guidewires, sheaths and catheters are disclosed infor example, Ye et al. (Transapical aortic valve implantation in humans.Ye J, Cheung A, Lichtenstein S V, Carere R G, Thompson C R, Pasupati S,Webb J G. J Thorac Cardiovasc Surg. 2006 May; 131(5):1194-6) andLichtenstein et al. (Transapical transcatheter aortic valve implantationin humans: initial clinical experience. Lichtenstein S V, Cheung A, YeJ, Thompson C R, Carere R G, Pasupati S, Webb J G. Circulation. 2006Aug. 8; 114 (6):591-6. Epub 2006 Jul. 31), the contents of each of whichare herein incorporated by reference.

Materials which may be used to construct the device comprisingreplacement heart valves are well known in the art, for example asdescribed in U.S. Publication No. US2011/0319989, which is incorporatedby reference herein in its entirety.

Methods

Disclosed are various embodiments of a method for transcatheter mitralvalve replacement. The method comprises the following steps: (1)identifying a subject having a double-orifice mitral valve; (2)providing a device as described above; and (3) delivering the device tothe double-orifice mitral valve.

Disclosed are various embodiments for a method for treating mitral valvediseases (such as MR, residual MR, or MS). The method comprises thefollowing steps: (1) performing an edge-to-edge repair of a mitral valvein a subject, thereby creating a double-orifice mitral valve; (2)providing a device as described above; and (3) delivering the device tothe double-orifice mitral valve.

Disclosed are various embodiments for a method for treating mitral valvediseases (such as MR, residual MR, or MS). The method comprises thefollowing steps: (1) performing an edge-to-edge repair of a mitral valvein a subject, thereby creating a double-orifice mitral valve; (2)assessing MR or MS in the subject after the edge-to-edge repair; (3) ifthe edge-to-edge repair does not effectively treat MR or MS in thesubject, providing a device as described above; and (4) delivering thedevice to the double-orifice mitral valve.

In various embodiments, the device is delivered transseptally ortransapically. In various embodiments, the subject is a human. Invarious embodiments, the subject is a mammal.

In various embodiments, the devices, systems and methods describedherein are configured for humans. One of skill in the art would readilyappreciate that the devices, systems and methods described herein couldbe customized for use in almost any mammal in which a heart valve may bereplaced. “Mammal” as used herein refers to any member of the classMammalia, including but not limited to, humans, domestic animals, farmanimals, zoo animals, sport animals, pet animals such as dogs, cats,guinea pigs, rabbits, rats, mice, horses, cattle, cows; primates such asapes, monkeys, orangutans, and chimpanzees; canids such as dogs andwolves; felids such as cats, lions, and tigers; equids such as horses,donkeys, and zebras; food animals such as cows, pigs, and sheep;ungulates such as deer and giraffes; rodents such as mice, rats,hamsters and guinea pigs; and so on. In certain embodiments, the mammalis a human subject. The term does not denote a particular age or sex.Thus, adult, newborn, fetuses, male or female mammalian heart surgery iswithin the scope of this disclosure.

Also in accordance with the present invention, as regular TMVR is aknown surgical procedure, one of ordinary skill in the art would readilyrecognize that the method could involve other additional steps, whichare not described in details here. These additional steps include, butare not limited to, anesthesia, sterilization, heparinization, accessingthe patient's heart via various routes such as femoral, transseptal,transaortic and transapical approaches, ventricular pacing, stitching ofthe access site or percutaneous femoral closure. For example, moreinformation on these procedures are described in Masson et al.(Percutaneous treatment of mitral regurgitation; Circ Cardiovasc Interv.2009 April; 2(2):140-6) and Chiam et al. (Percutaneous transcathetermitral valve repair: a classification of the technology; JACC CardiovascInterv. 2011 Jan. 4(1):1-13), each of which is incorporated herein byreference in its entirety.

EXAMPLES

The following examples are provided to better illustrate the claimedinvention and are not to be interpreted as limiting the scope of theinvention. To the extent that specific materials are mentioned, it ismerely for purposes of illustration and is not intended to limit theinvention. One skilled in the art may develop equivalent means orreactants without the exercise of inventive capacity and withoutdeparting from the scope of the invention.

Example 1

Repair of the mitral valve using the edge-to-edge technique can beperformed surgically (e.g., Alfieri stitch) or percutaneously (e.g.,EDWARDS LIFESCIENCES' MOBIUS and ABBOTT's MITRACLIP). It involvesjoining or bringing together the middle of the anterior and posteriorleaflets of the mitral valve, thereby making a single orifice a doubleorifice. This is intended to reduce the gap between the two leafletsthat can occur during systole in pathological states that often causesMR.

Although edge-to-edge repair can achieve excellent results in MR, it hasstrict anatomical criteria for case selection that limits the number ofpatients that qualify for it. Moreover, the failure rate of thisprocedure remains relatively high. Currently, failure of edge-to-edgerepair is addressed either by medical therapy in inoperable patients orsurgical revision in those who are operable. However, there is presentlyno percutaneous option for such patients.

In some embodiments, the presently disclosed DO-TMVR methods, devices,and systems solve these problems. For example, implantation of a DO-TMVRcan be used to treat patients who have had a failed edge-to-edge mitralvalve repair procedure for severe mitral regurgitation (MR).

In some embodiments, the design of DO-TMVR utilizes the double orificeof the mitral valve as a reliable tissue anchor and to provide a sealaround the device. Also, if treatment of MR with a DO-TMVR is anavailable option, then edge-to-edge repair procedures, rather thanhaving strict anatomical criteria for case selection, could be attemptedin a broader group of patients. This is because if an edge-to-edgerepair failed, DO-TMVR could still be employed to remedy the defectivevalve.

Implantation of the presently disclosed DO-TMVR device may be performedantegradely (from femoral vein to RA to transseptal puncture to LA tomitral valve) or retrogradely (from LV apex to LV to mitral valve). Insome embodiments, the DO-TMVR device includes two replacement valvesthat are mounted on a delivery catheter. The two replacement valves maybe separate or connected, and may be deployed separately or together.The two replacement valves may contain cylindrical stent structures andmay each carry one, two, three or more leaflets. The leaflets may bebiological or artificial. The stent structures may be made of nitinol orother alloys (e.g., stainless steel, cobalt-chromium, andplatinum-iridium). The two replacement valves may be self-expandable orballoon-expandable. As illustrated in FIG. 1D, each of the tworeplacement valves may be implanted into each of the two orifices of thedouble-orifice mitral valve created by an edge-to-edge repair.

Implantation of the presently disclosed DO-TMVR device could beperformed during an edge-to-edge repair procedure, or preferably at alater time, when scar tissue has formed over the edge-to-edge repair.Waiting until scar tissue has formed may ensure that there is a morereliable tissue scaffold for an anchor, and may also prevent scar tissueformation from interfering with the valve fit or operation.

Example 2 Transseptal Balloon-Expandable DO-TMVR

FIGS. 2A-E illustrate an example of a transseptal DO-TMVR procedureusing one of the presently disclosed devices. In some embodiments, afterinduction of anesthesia and sterile preparation, an incision is made inthe femoral leg vein. Alternatively, percutaneous femoral access isperformed with or without pre-closure. In some embodiments, atransseptal catheter 208 is advanced over a wire and inserted to theright atrium from the femoral leg vein, via the inferior vena cava(IVC), to the right atrium (RA) and placed in close proximity to theinter-atrial septum. Then, the guidewire may be removed. As illustratedin FIG. 2A, in some embodiments, a transseptal puncture needle (shown asan arrow in FIG. 2A) may then be advanced through the transseptalcatheter. The transseptal puncture needle may then be utilized topuncture the heart septum from RA to left atrium (LA). Then, thetransseptal catheter may then be inserted over the transseptal needlethrough the puncture of the interatrial septum. The transseptal punctureneedle may then be withdrawn via the transseptal catheter out of thepatient's body, leaving only the transseptal catheter in the leftatrium. Following this, the transseptal catheter may be exchanged for asheath 203 (which may be of 12 Fr-24 Fr) by wire exchange. Asillustrated in FIG. 2B, two guide wires 201 and 202 (which may be of110-260 cm length and 0.018″-0.038″ caliber) may then be inserted intothe sheath 203 and further across each orifice of the double-orificemitral valve.

In some embodiments, a delivery catheter 204 (which may be 12 Fr-24 Fr)having an inverted Y-shaped inflatable balloon 205 at its distal end maythen be inserted over the two guide wires (201 and 202) and into thesheath 203. The first and second replacement valves (101 and 102) of aDO-TMVR device may then be mounted on the two end branches of theinverted Y-shaped inflatable balloon 205. In this example, the tworeplacement valves (101 and 102) are connected via a connector 103 suchas a hinge prior to delivery. In some embodiments, the two replacementvalves (101 and 102) are connected via a connector 103 such as a hingeduring the manufacturing process and are loaded onto the deliverycatheter 204 as two connected valves. In some embodiments, prior todelivery and while loaded into the delivery catheter 204 the tworeplacement valves (101 and 102) are in compressed state inside thecatheter and an inverted Y-shaped inflatable balloon is deflated. Asillustrated in FIG. 2C, the delivery catheter 204 is guided to thedouble-orifice mitral valve so that a replacement valve (101 and/or 102)is placed in each orifice. Then, the inverted Y-shaped inflatableballoon may be inflated to expand the two replacement valves (101 and102). As illustrated in FIG. 2D, as a result, a seal is formed betweenthe two replacement valves (101 and 102) and the double-orifice mitralvalve, and on the atrial side, the connector 103 such as a hinge isanchored or sits on top of the middle portion of the anterior andposterior leaflets that has been surgically connected. As illustrated inFIG. 2E, the inverted Y-shaped inflatable balloon may then be deflatedand the delivery catheter may be withdrawn via the sheath out of thepatient's body. Following, the two guide wires (201 and 202) may bewithdrawn via the sheath 203 out of the patient's body. Additionalstandard steps that may be performed during the procedure may includeheparinization and closure of the femoral vein either by manualcompression, suture-mediated pre-closure or surgical closure. Theprocedure may be performed with local anesthesia with conscious sedationor general anesthesia. Heparinization may be reversed at the end of theprocedure by administration of protamine. Heparin intolerant individualsmay be anticoagulated during the procedure using direct thrombininhibitors.

Example 3 Transapical Balloon-Expandable DO-TMVR

FIGS. 3A-3E illustrate a further example of an implantation procedureutilizing a transapical DO-TMVR device. After induction of anesthesia,and sterile preparation, an apical incision may be performed by astandard procedure as described in for example, Lichtenstein et al.Transapical transcatheter aortic valve implantation in humans: initialclinical experience. Circulation. 2006 Aug. 8; 114(6):591-6. Epub 2006Jul. 31, which is incorporated by reference herein in its entirety.

In some embodiments, the apex of the heart may be exposed for thesurgical approach or punctured with a needle directly under ultrasoundguidance for a percutaneous approach. For a surgical approach, pledgetedsutures may be placed in a ring over the left ventricle (LV) apicalsurface. An example of a percutaneous approach is described in Dudiy etal. Percutaneous closure of left ventricular pseudoaneurysm, CircCardiovasc Interv. 2011 August; 4(4):322-6. Epub 2011 Jul. 26, which isincorporated by reference herein in its entirety.

FIG. 3A illustrates a needle of gauge 12-16, or other suitable gauges,that may be utilized to puncture the LV apex. In some embodiments, afterthe puncture of the LV apex, a first guide wire 201 of caliber0.014″-0.038″ may be inserted through the needle, into LV, through oneof the two orifices of the double-orifice mitral valve, and into LA.Then, the needle may be withdrawn. A sheath of size 4-7 Fr is inserted,and exchanged over a 0.035″ or 0.038″ wire to another sheath 203 of size12-24 Fr, which is inserted over the guide wire (201 and/or 202) intoLV. FIG. 3B illustrates a second guide wire 202 being inserted into thesheath 203, into LV, through the other of the two orifices of thedouble-orifice mitral valve and into LA.

Next, a delivery catheter 204 (which may be 12 Fr-24 Fr) having aninverted Y-shaped inflatable balloon 205 at its distal end may beinserted over the two guide wires (201 and 202) and into the sheath 203.Then, the first and second replacement valves (101 and 102) of DO-TMVRdevice may be mounted on the two end branches of the inverted Y-shapedinflatable balloon 205. In this example, the two replacement valves (101and 102) may be connected via a connector 103 such as a hinge prior todelivery. The two replacement valves (101 and 102) are already connectedvia a connector 103 such as a hinge during the manufacturing process andare loaded onto the delivery catheter 204 as two connected valves. Whileloaded into the delivery catheter 204, the two replacement valves (101and 102) are in compressed status and the inverted Y-shaped inflatableballoon is deflated. FIG. 3C illustrates the delivery catheter 204 beingguided to the double-orifice mitral valve so that a replacement valve(101 and 102) is placed in each orifice. The inverted Y-shapedinflatable balloon may then be inflated to expand the two replacementvalves (101 and 102). As illustrated in FIG. 3D, after inflation of thevalves (101 and 102), a seal is formed between the two replacementvalves (101 and 102) and the double-orifice mitral valve, and on theventricular side, the connector 103 such as a hinge may be anchoredbelow the connected middle of the anterior and posterior leaflets 106.As illustrated in FIG. 3E, the inverted Y-shaped inflatable balloon maythen be deflated and the delivery catheter 204 may then be withdrawn viathe sheath 203 and out of the patient's body. Then, the two guide wires(201 and 202) may be withdrawn via the sheath 203 out of the patient'sbody, and then the sheath 203 itself is withdrawn out of the patient'sbody. During the procedure, additional standard steps may be performedsuch as heparinization and/or closure of the apex either surgically orutilizing a transcatheter approach with an Amplatzer or dedicatedclosure device. The procedure is performed under general anesthesia andthe patient is generally woken up immediately after the procedure.Heparinization may be reversed at the end of the procedure byadministration of protamine. Heparin intolerant individuals may beanticoagulated during the procedure using direct thrombin inhibitors.

Example 4 Transseptal Self-Expandable DO-TMVR

FIGS. 4A-4D illustrate an example of a transseptal implantationprocedure for a DO-TMVR a device as disclosed herein. After induction ofanesthesia, and sterile preparation, an incision is performed at thefemoral leg vein. Alternatively, percutaneous femoral access may beperformed with or without pre-closure. A transseptal catheter 208 maythen be advanced over a wire 201 and/or 202 and inserted to the rightatrium from the femoral leg vein, via inferior vena cava (IVC), to theright atrium (RA) and placed close to the inter-atrial septum. The wire201 and/or 202 may then be removed. As illustrated in FIG. 4A, atransseptal puncture needle may then be advanced through the transseptalcatheter. In some embodiments, the transseptal puncture needle may beutilized to puncture the heart septum from RA to left atrium (LA). Afterpuncture of the heart septum, the transseptal catheter may then beinserted over the transseptal needle through the puncture of the septum.The transseptal puncture needle may then be withdrawn via thetransseptal catheter out of the patient's body, leaving only thetransseptal catheter in the left atrium. The transseptal catheter 208may then be exchanged for a sheath 203 (which may be of 12 Fr-24 Fr) bywire exchange. As illustrated in FIG. 4B, two guide wires 201 and 202(which may be of 110-260 cm length and 0.018″-0.038″ caliber) may thenbe inserted into the sheath 203 and further across each orifice of thedouble-orifice mitral valve.

As shown in FIGS. 4C-D, a delivery catheter 206 (which may be 12-24 Fr)having an inverted Y-shaped enclosing sheath 207 at its distal end isinserted over the two guide wires (201 and 202) and into the sheath 203.In the delivery catheter 208, two catheters 210 and 211 are insertedinto a cover 209 and over the two guide wires 201 and 202. The first andsecond replacement valves (101 and 102) of a DO-TMVR device may then becompressed and mounted near the distal ends of the two catheters 210 and211. Then, distal to the two replacement valves 101 and 102, twoenclosing caps 212 and 213 may be placed at the distal ends of the twocatheters 210 and 211. In some embodiments, the two enclosing caps 212and 213 enclose the two replacement valves 101 and 102 to keep themcompressed. In this example, the two replacement valves may be connectedvia a connector 103 such as a hinge prior to delivery. The tworeplacement valves (101 and 102) are already connected via a connectingmeans 103 such as a hinge during the manufacturing process and areloaded onto the delivery catheter 208 as two connected valves. Asillustrated in FIG. 4C, the delivery catheter 208 is guided to thedouble-orifice mitral valve so that a replacement valve (101 and 102) isplaced in each orifice. In some embodiments, the two catheters 210 and211 are advanced to expand the two replacement valves (101 and 102). Asillustrated in FIG. 4E, after expansion of the replacement valves (101and 102), a seal is formed between the two replacement valves (101 and102) and the double-orifice mitral valve, and on the atrial side, theconnector 103 such as a hinge is anchored over the connected middle ofthe anterior and posterior leaflets 106. The delivery catheter 204 iswithdrawn via the sheath 203 out of the patient's body; the two guidewires (201 and 202) may be withdrawn via the sheath out of the patient'sbody; and the sheath 203 is withdrawn out of the patient's body.Additional standard steps that may be performed during the procedureinclude heparinization, and closure of the femoral vein either by manualcompression, suture-mediated pre-closure or surgical closure. Theprocedure may be performed by local anesthesia with conscious sedationor general anesthesia, in which case the patient is generally woken upimmediately after the procedure. Heparinization may be reversed at theend of the procedure by administration of protamine. Heparin intolerantindividuals may be anticoagulated during the procedure using directthrombin inhibitors.

Example 5 Transapical Self-Expandable DO-TMVR

FIGS. 5A-E illustrate an example of transapical implantation of aDO-TMVR device. After induction of anesthesia, and sterile preparation,an apical incision may be performed by a standard procedure as describedin Lichtenstein et al. Transapical transcatheter aortic valveimplantation in humans: initial clinical experience. Circulation. 2006Aug. 8; 114(6):591-6. Epub 2006 Jul. 31, which is incorporated byreference herein in its entirety.

In order to perform the procedure, the apex of the heart may be exposedfor a surgical approach or punctured with a needle using a percutaneousapproach. If a surgical approach is utilized, pledgeted sutures may beplaced in a ring over the left ventricle (LV) apical surface. Thepercutaneous approach may be performed, for example, as described inDudiy et al. Percutaneous closure of left ventricular pseudoaneurysm,Circ Cardiovasc Interv. 2011 August; 4(4):322-6. Epub 2011 Jul. 26,which is incorporated by reference herein in its entirety.

As illustrated in FIG. 5A, a needle of gauge 12-16 (shown as an arrow inFIG. 5A) may be utilized to puncture the LV apex. As illustrated in FIG.5A, after puncture of the apex, a first guide wire 201 of caliber0.014″-0.038″ may be inserted through the needle, into LV, through oneof the two orifices of the double-orifice mitral valve, and into LA. Theneedle may then be withdrawn. A sheath of size 4-7 Fr is inserted, andexchanged over a 0.035″ or 0.038″ wire to another sheath 203 of size12-24 Fr, which is inserted over the guide wire into LV. As illustratedin FIG. 5B, a second guide wire 202 may be inserted into the sheath 203,into LV, through the other of the two orifices of the double-orificemitral valve and into LA.

As shown in FIGS. 5C-D, a delivery catheter 206 (which may be 12-24 Fr)having an inverted Y-shaped enclosing sheath 207 at its distal end maybe inserted over the two guide wires (201 and 202) and into the sheath(203). In the delivery catheter 204, two catheters 210 and 211 areinserted into a cover 209 and over the two guide wires 201 and 202. Thefirst and second replacement valves (101 and 102) of DO-TMVR device arecompressed and mounted near the distal ends of the two catheters 210 and211. Further distal to the two replacement valves 101 and 102, twoenclosing caps 212 and 213 are placed at the distal ends of the twocatheters 210 and 211. The two enclosing caps 212 and 213 may enclosethe two replacement valves 101 and 102 in order to keep them compressed.In this example, the two replacement valves 101 and 102 are connectedvia a connector 103 such as a hinge prior to delivery. The tworeplacement valves 101 and 102 are already connected via a connector 103such as a hinge during the manufacturing process and are loaded onto thedelivery catheter 204 as two connected valves 101 and 102. Asillustrated FIG. 5C, the delivery catheter 204 is guided to thedouble-orifice mitral valve so that a replacement valve 101 and 102 isplaced in each orifice. In some embodiments, the two catheters 210 and211 are advanced to allow the two replacement valves 101 and 102 toexpand. As illustrated in FIG. 5E, after of the expansion of the valves101 and 102, a seal is formed between the two replacement valves 101 and102 and the double-orifice mitral valve, and on the ventricular side,the connector 103 such as a hinge is anchored under the connected middleof the anterior and posterior leaflets. Then, the delivery catheter maybe withdrawn via the sheath 203 out of the patient's body; the two guidewires 201 and 202 withdrawn via the sheath 203 out of the patient'sbody; and the sheath 203 is withdrawn out of the patient's body.Additionally, during the procedure, standard steps may be performedincluding heparinization and surgical closure of the apex, or bytranscatheter approach with an Amplatzer or dedicated closure device.The procedure may be performed under general anesthesia. Heparinizationmay be reversed at the end of the procedure by administration ofprotamine. Heparin intolerant individuals may be anticoagulated duringthe procedure using direct thrombin inhibitors.

The various methods and techniques described above provide a number ofways to carry out the application. Of course, it is to be understoodthat not necessarily all objectives or advantages described can beachieved in accordance with any particular embodiment described herein.Thus, for example, those skilled in the art will recognize that themethods can be performed in a manner that achieves or optimizes oneadvantage or group of advantages as taught herein without necessarilyachieving other objectives or advantages as taught or suggested herein.A variety of alternatives are mentioned herein. It is to be understoodthat some preferred embodiments specifically include one, another, orseveral features, while others specifically exclude one, another, orseveral features, while still others mitigate a particular feature byinclusion of one, another, or several advantageous features.

Furthermore, the skilled artisan will recognize the applicability ofvarious features from different embodiments. Similarly, the variouselements, features and steps discussed above, as well as other knownequivalents for each such element, feature or step, can be employed invarious combinations by one of ordinary skill in this art to performmethods in accordance with the principles described herein. Among thevarious elements, features, and steps some will be specifically includedand others specifically excluded in diverse embodiments.

Although the application has been disclosed in the context of certainembodiments and examples, it will be understood by those skilled in theart that the embodiments of the application extend beyond thespecifically disclosed embodiments to other alternative embodimentsand/or uses and modifications and equivalents thereof.

In some embodiments, the terms “a” and “an” and “the” and similarreferences used in the context of describing a particular embodiment ofthe application (especially in the context of certain of the followingclaims) can be construed to cover both the singular and the plural. Therecitation of ranges of values herein is merely intended to serve as ashorthand method of referring individually to each separate valuefalling within the range. Unless otherwise indicated herein, eachindividual value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (for example, “such as”) provided withrespect to certain embodiments herein is intended merely to betterilluminate the application and does not pose a limitation on the scopeof the application otherwise claimed. No language in the specificationshould be construed as indicating any non-claimed element essential tothe practice of the application.

Preferred embodiments of this application are described herein,including the best mode known to the inventors for carrying out theapplication. Variations on those preferred embodiments will becomeapparent to those of ordinary skill in the art upon reading theforegoing description. It is contemplated that skilled artisans canemploy such variations as appropriate, and the application can bepracticed otherwise than specifically described herein. Accordingly,many embodiments of this application include all modifications andequivalents of the subject matter recited in the claims appended heretoas permitted by applicable law. Moreover, any combination of theabove-described elements in all possible variations thereof isencompassed by the application unless otherwise indicated herein orotherwise clearly contradicted by context.

All patents, patent applications, publications of patent applications,and other material, such as articles, books, specifications,publications, documents, things, and/or the like, referenced herein arehereby incorporated herein by this reference in their entirety for allpurposes, excepting any prosecution file history associated with same,any of same that is inconsistent with or in conflict with the presentdocument, or any of same that may have a limiting affect as to thebroadest scope of the claims now or later associated with the presentdocument. By way of example, should there be any inconsistency orconflict between the description, definition, and/or the use of a termassociated with any of the incorporated material and that associatedwith the present document, the description, definition, and/or the useof the term in the present document shall prevail.

It is to be understood that the embodiments of the application disclosedherein are illustrative of the principles of the embodiments of theapplication. Other modifications that can be employed can be within thescope of the application. Thus, by way of example, but not oflimitation, alternative configurations of the embodiments of theapplication can be utilized in accordance with the teachings herein.Accordingly, embodiments of the present application are not limited tothat precisely as shown and described.

What is claimed is:
 1. A method comprising: identifying a subject havinga double-orifice mitral valve; providing a device for transcathetermitral valve replacement, comprising: a first replacement heart valvehaving a first atrial side and a first ventricular side; and a secondreplacement heart valve having a second atrial side and a secondventricular side, wherein the first and second replacement heart valvesare connected with a hinge, and each of the first and second replacementheart valves are substantially equivalent in size and sized toseparately fit in one orifice of a human double orifice mitral valve andconfigured to fit together in a double orifice mitral valve created byan edge-edge repair when connected to the hinge, and delivering thedevice to the double-orifice mitral valve such that each of the firstand second replacement heart valves are placed within a respectiveorifice of the double-orifice mitral valve.
 2. The method of claim 1,wherein the first and second replacement heart valves are connected ontheir atrial and/or ventricular sides with the hinge.
 3. The method ofclaim 1, wherein the first and second replacement heart valves are notdirectly connected to each other.
 4. The method of claim 1, wherein thefirst and second replacement heart valves do not extend from each other.5. The method of claim 1, wherein the first and second replacement heartvalves are not held together by a frame or gasket.
 6. The method ofclaim 1, wherein no frame or gasket surround the first and secondreplacement heart valves.
 7. The method of claim 1, wherein the firstreplacement heart valve is a prosthetic valve or a bio-prosthetic valveand the second replacement heart valve is a prosthetic valve or abio-prosthetic valve.
 8. The method of claim 1, wherein the firstreplacement heart valve is self-expandable or balloon expandable and thesecond replacement heart valve is self-expandable or balloon expandable.9. The method of claim 1, wherein the cross section of the firstreplacement valve is a circle or ellipse and the cross section of thesecond replacement valve is a circle or ellipse.
 10. The method of claim1, wherein the cross sections of the first and second replacement heartvalves are two D-shapes with their straight sides opposing each other.11. The method of claim 1, wherein the first replacement heart valvecomprises stent frames made of iron, platinum, titanium, nickel,chromium, cobalt, magnesium, stainless steel, nitinol (nickel-titanium),nickel-chromium, cobalt-chromium, or platinum-iridium, or a combinationthereof.
 12. The method of claim 1, wherein the second replacement heartvalve comprises stent frames made of iron, platinum, titanium, nickel,chromium, cobalt, magnesium, stainless steel, nitinol (nickel-titanium),nickel-chromium, cobalt-chromium, or platinum-iridium, or a combinationthereof.
 13. The method of claim 1, wherein the first replacement heartvalve comprises one, two, three, or more leaflets and the secondreplacement heart valve comprises one, two, three, or more leaflets. 14.The method of claim 1, further comprising a delivery catheter.
 15. Themethod of claim 14, wherein the delivery catheter has an invertedY-shaped inflatable balloon at its distal end.
 16. The method of claim15, wherein the delivery catheter has an inverted Y-shaped enclosingsheath at its distal end.
 17. The method of claim 1, further comprisingtwo guide wires, wherein a delivery catheter can be inserted over thetwo guide wires.
 18. The method of claim 1, further comprising a sheath,wherein a delivery catheter can be inserted into the sheath.
 19. Themethod of claim 1, wherein the device is delivered transseptally ortransapically.
 20. A method, comprising: performing an edge-to-edgerepair of a mitral valve in a subject, thereby creating a double-orificemitral valve; providing a device, the device comprising: a firstreplacement heart valve having a first atrial side and a firstventricular side; and a second replacement heart valve having a secondatrial side and a second ventricular side, wherein the first and secondreplacement heart valves are connected with a hinge, and each of thefirst and second replacement heart valves are substantially equivalentin size and sized to separately fit in one orifice of the double-orificemitral valve and configured to fit together in the double orifice mitralvalve when connected to the hinge; and delivering the device to thedouble-orifice mitral valve such that each of the first and secondreplacement heart valves are placed within a respective orifice of thedouble-orifice mitral valve.
 21. The method of claim 20, wherein thedevice is delivered transseptally or transapically.
 22. A method,comprising: performing an edge-to-edge repair of a mitral valve in asubject, thereby creating a double-orifice mitral valve; assessingmitral regurgitation in the subject after the edge-to-edge repair; andif the edge-to-edge repair does not effectively treat mitralregurgitation in the subject, providing a device, the device comprising:a first replacement heart valve having a first atrial side and a firstventricular side; and a second replacement heart valve having a secondatrial side and a second ventricular side, wherein the first and secondreplacement heart valves are connected with a hinge, and each of thefirst and second replacement heart valves are substantially equivalentin size and sized to separately fit in one orifice of the double orificemitral valve and configured to fit together in the double orifice mitralvalve when connected to the hinge and delivering the device to thedouble orifice mitral valve such that each of the first and secondreplacement heart valves are placed within a respective orifice of thedouble-orifice mitral valve.
 23. The method of claim 22, wherein thedevice is delivered transseptally or transapically.
 24. The method ofclaim 22, wherein the cross sections of the first and second replacementheart valves are circular shaped.